载姜黄素/阿霉素叶酸偶联壳聚糖纳米粒的制备

Preparation of Folate Modified Chitosan Nanoparticles Loaded with Curcumin and Adriamycin

姜黄素(CUR)是一种天然植物多酚,具有逆转肿瘤多药耐药的功效,与抗癌药物阿霉素(DOX)联合用药可以提高阿霉素对肿瘤细胞的敏感性,从而逆转肿瘤多药耐药性。以壳聚糖为载体,叶酸为靶向受体,三聚磷酸钠(TPP)为聚阴离子,姜黄素与阿霉素为药物模型,利用阴阳离子间的静电相互作用,制备了叶酸偶联壳聚糖载双药纳米粒,以达到纳米粒同时具有肿瘤靶向性和抗多药耐药的双重目的。目标产物通过红外光谱、SEM、Zeta电位仪表征了结构和形态,同时考察了不同反应条件对生成纳米粒的影响。结果显示在适宜反应条件(偶联叶酸的壳聚糖浓度和TPP的浓度分别为2.5 mg/m L和1 mg/m L,反应温度25℃,搅拌速度500 r/min,反应体系p H为5.0~6.0)下,得到载药纳米粒粒径约190 nm,Zeta电位为30.72 m V,阿霉素和姜黄素的包封率分别可达85.7%和93.9%,相比目前其他的一些双载药纳米粒,包封率具有明显的提高。

Curcumin( CUK) is a kind of natural plant polyphenol,has been confirmed with the effect of reversing multidrug resistance of tumor,combination with adriamycin can improve the sensitivity of adriamycin on tumor cell,and reversing multidrug resistance of tumor. With chitosan as the carrier,folic acid for the targeted receptor,sodium tripolyphosphate as polyanion,curcumin and adriamycin as drug model,and using the ion electrostatic interaction between cations and anions,that folate conjugated chitosan loaded double drug nanoparticles were prepared to achieve the dual purpose with tumor targeting and multidrug resistance at the same time. The target products are characterized by means of FTIR,SEM and Zeta potential analyzer,the effects of different reaction conditions on the formation of nanoparticles were also investigated. The results show that under the optimum conditions of c( coupling of folic acid of chitosan) 2. 5 mg/m L,c( TPP) 1 mg/m L,reaction temperature 25 ℃,stirring speed500 r/min,p H of reaction system 5. 0 ~ 6. 0,the size of nanoparticles about 190 nm,Zeta potential 30. 72 m V.The entrapment efficiencies of DOX and CUR were 85. 7% and 93. 9%,respectively. Compared with some other double drug loaded nanoparticles,the encapsulation efficiency is obviously improved.